Design, synthesis, and therapeutic potential of pyridazinone-based molecules: An updated comprehensive review

Abstract

Drug discovery involves the design, synthesis and pharmacological evaluation of new chemical entities. Heterocyclic compounds are ring structures in which a carbon atom is replaced by heteroatoms such as oxygen, nitrogen, phosphorus, or sulfur. Much attention has been directed toward heterocyclic compounds due to their broad spectrum of biological activities, such as antimicrobial, anti-inflammatory, anticancer, and antiviral properties. Among these, pyridazinone-based molecules have attracted considerable attention due to their wide range of pharmacological and agrochemical applications. The chemical synthesis of pyridazinone derivatives was first described by Schmidt and Druey in 1954, using classical methods such as the condensation of hydrazine derivatives with carbonyl compounds. Through appropriate functionalization, the inherent reactivity of the pyridazinone core has been exploited to enhance the pharmacological profiles of various bioactive molecules. The pyridazinone derivatives have expressed various kinds of biological activities: anticancer, anti-inflammatory, analgesic, antimicrobial, neuroprotective, cardiovascular, and anticonvulsant properties. This review presents a systematic evaluation of pyridazinone derivatives, highlighting advances reported from 2010 to 2024. Particular emphasis is given to innovative synthetic methodologies, with discussion of their reaction mechanisms and applicability for structural modification The pharmacological profile covers structure-activity relationships, molecular targets, mechanisms of action, and recent data on potency, selectivity, and toxicity. Despite progress, challenges persist in developing pyridazinone-based therapeutics, especially concerning bioavailability and target specificit. Future research directions are proposed, considering emerging strategies in medicinal chemistry and drug design. This work intends to serve as a reference for researchers working toward new pyridazinone derivatives with improved pharmacological properties.